Chimeric antigen receptor T-cell (CAR-T) therapy is the result of combining genetic engineering-based cancer immunotherapy with adoptive cell therapy (ACT). CAR-T therapy has been successful in treating various types of hematological cancers. CARs are receptors made of an extracellular domain, a membrane-spanning domain, and an intracellular domain. The extracellular domain of CARs harbors an antigen-targeting domain responsible for recognizing and binding cell surface-expressed target antigens. Conventionally, the single-chain fragment variable (scFv) of a monoclonal antibody (mAb) is used as the antigen-targeting domain of CARs. However, of late, researchers have exploited nanobodies for this aim based on numerous rationales including the small size of nanobodies, their stability, specificity, and high affinity, and their easy and feasible development process. Many findings have confirmed that nanobody-based CAR-Ts can be as functional as scFv-based CAR-Ts in preclinical and clinical settings. In this review, we discuss the advantages and disadvantages of scFvs and nanobodies in regards to their application as the targeting domain of CARs. Ultimately, we discuss various CAR target antigens which have been targeted using nanobody-based CAR-T cells for the treatment of different types of malignancies.
Natural bioactive compounds with antioxidant activity play remarkable roles in the prevention of reactive oxygen species (ROS) formation. ROS, which are formed by different pathways, have various pathological influences such as DNA damage, carcinogenesis, and cellular degeneration. Incremental demands have prompted the search for newer and alternative resources of natural bioactive compounds with antioxidant properties. The marine environment encompasses almost three-quarters of our planet and is home to many eukaryotic and prokaryotic microorganisms. Because of extreme physical and chemical conditions, the marine environment is a rich source of chemical and biological diversity, and marine microorganisms have high potential as a source of commercially interesting compounds with various pharmaceutical, nutraceutical, and cosmeceutical applications. Bacteria and microalgae are the most important producers of valuable molecules including antioxidant enzymes (such as superoxide dismutase and catalase) and antioxidant substances (such as carotenoids, exopolysaccharides, and bioactive peptides) with various valuable biological properties and applications. Here, we review the current knowledge of these bioactive compounds while highlighting their antioxidant properties, production yield, health-related benefits, and potential applications in various biological and industrial fields.
1 May 2020 in International Journal of Biological Macromolecules
Triple-negative breast cancer (TNBC) is known as the most intricate and hard-to-treat subtype of breast cancer. TNBC cells do not express the well-known estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expressed by other breast cancer subtypes. This phenomenon leaves no room for novel treatment approaches including endocrine and HER2-specific antibody therapies. To date, surgery, radiotherapy, and systemic chemotherapy remain the principal therapy options for TNBC treatment. However, in numerous cases, these approaches either result in minimal clinical benefit or are nonfunctional, resulting in disease recurrence and poor prognosis. Nowadays, chimeric antigen receptor T cell (CAR-T) therapy is becoming more established as an option for the treatment of various types of hematologic malignancies. CAR-Ts are genetically engineered T lymphocytes that employ the body’s immune system mechanisms to selectively recognize cancer cells expressing tumor-associated antigens (TAAs) of interest and efficiently eliminate them. However, despite the clinical triumph of CAR-T therapy in hematologic neoplasms, CAR-T therapy of solid tumors, including TNBC, has been much more challenging. In this review, we will discuss the success of CAR-T therapy in hematological neoplasms and its caveats in solid tumors, and then we summarize the potential CAR-T targetable TAAs in TNBC studied in different investigational stages.
Chimeric antigen receptor T-cells (CAR-Ts) are known as revolutionary living drugs that have turned the tables of conventional cancer treatments in certain hematologic malignancies such as B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL) by achieving US Food and Drug Administration (FDA) approval based on their successful clinical outcomes. However, this type of therapy has not seen the light of victory in the fight against solid tumors because of various restricting caveats including heterogeneous tumor antigen expression and the immunosuppressive tumor microenvironments (TME) that negatively affect the tumor-site accessibility, infiltration, stimulation, activation, and persistence of CAR-Ts. In this review, we explore strategic twists including boosting vaccines and designing implementations that can support CAR-T expansion, proliferation, and tumoricidal capacity. We also step further by underscoring novel strategies for triggering endogenous antitumor responses and overcoming the limitation of poor CAR-T tumor-tissue infiltration and the lack of definitive tumor-specific antigens. Ultimately, we highlight how these approaches can address the mentioned arduous hurdles.
Chimeric antigen receptor T-cell (CAR-T) therapy has been prosperous in the treatment of patients with various types of relapsed/refractory (R/R) B-cell malignancies including diffuse large B-cell lymphoma (DLBCL), B-cell acute lymphoblastic leukemia (B-ALL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and multiple myeloma (MM). However, this type of therapy has faced serious hindrances in combating T-cell neoplasms. R/R T-cell malignancies are generally associated with poor clinical outcomes, and the available effective treatment approaches are very limited. CAR-T therapy of T-cell malignancies has unique impediments in comparison with that of B-cell malignancies. Fratricide, T-cell aplasia, and product contamination with malignant T cells when producing autologous CAR-Ts are the most important challenges of CAR-T therapy in T-cell malignancies necessitating in-depth investigations. Herein, we highlight the preclinical and clinical efforts made for addressing these drawbacks and also review additional potent stratagems that could improve CAR-T therapy in T-cell malignancies.